Transport and Metabolism tissues in addition to exerting negative feedback on the pituitary and hypothalamus. The major binding protein is thyroxine-binding globulin (TBG), which is synthesized Secreted T4 and T3 circulate in the bloodstream almost in the liver and binds one molecule of T4 or T3. About 70% entirely bound to proteins. Normally only about 0.03% of circulating T4 and T3 is bound to TBG; 10% to 15% of total plasma T4 and 0.3% of total plasma T3 exist in is bound to another specific thyroid-binding protein called the free state (
Fig. 42.8 ). Free T3 is biologically active and transthyretin (TTR). Albumin binds 15% to 20%, and mediates the effects of thyroid hormone on peripheral 3% is bound to lipoproteins. Ordinarily only alterations in ).CirculatingthyroidhormonesfeedbackonthepituitaryglandtodecreaseTSHsecretion,primarilybyrepressingTSHβ subunitgeneexpression.Thepituitaryglandexpressesthehigh-affinityD2,whichconvertsT4enteringthesecellstoT3.ThusfeedbackinthyrotropesmediatedbyintracellularT3representsanintegratedmeasureofcirculatingfreeT4andT3(see ).BecausethediurnalvariationinTSHsecretionissmall,thyroidhormonesecretionandplasmaconcentrationsarerelativelyconstant.OnlysmallnocturnalincreasesinsecretionofTSHandreleaseofT4occur.Thyroidhormonesalsofeedbackonhypothalamicthyroid-releasinghormone(TRH)secretingneurons.Intheseneurons,T3inhibitsexpressionoftheprepro-TRHgene.
Autoregulationofthyroidglandfunctioniscausedbyiodideitself,whichhasabiphasicaction.Atrelativelylowlevelsofiodideintake,therateofthyroidhormonesynthesisisdirectlyrelatedtotheavailabilityofiodide.However,iftheintakeofiodideexceeds2mg/day,theintraglandularconcentrationofiodidereachesalevelthatparadoxicallysuppressesTPOactivity,blockinghormonebiosynthesis.ThisphenomenonisknownastheWolff-Chaikoff effect. AdaptationtohighiodideintakenormallyoccursbyreducingexpressionofNIS,whichcausestheintrathyroidaliodideleveltofall.TPOactivitythenreturnstonormal,andthyroidhormonesynthesisresumeswithindaystoweeks.Inunusualinstances,failureofNIStodownregulateleadstoprolongedinhibitionofhormonesynthesisbyiodideandresultanthypothyroidism.Thetemporaryreductioninhormonesynthesisbyexcessiodidehasalsobeenusedtherapeuticallyinhyperthyroidism.
Becauseofitsabilitytotrap andincorporateiodineintothyroglobulin(calledorganification),theactivityofthethyroidcanbeassessedbyradioactive iodine uptake (RAIU). Inthistestatracerdoseof123IisadministeredandRAIUismeasuredbyplacingagammadetectorontheneckat4to6hoursandat24hours.IntheUnitedStates,wherethedietisrelativelyrichiniodine,RAIUistypicallyaround15%after6hoursand25%after24hours(